Amino acids are an essential building block of all life. Fluorinated versions are important, as they enable the study and probing of biological systems. Additionally, the inclusion of fluorine often modifies the properties in interesting ways which may confer desirable traits to a fluorinated analog. For instance, fluorination can result in resistance to oxidative cleavage within drug molecules resulting in longer circulation times of the molecules. The effect of fluorine is vast and beyond the scope here, but this is why year after year the number of FDA approved drugs that contain fluorine continue to rise; currently about 33% of new drugs contain fluorine.
Incorporation of unnatural amino acids into proteins has been an informative yet powerful approach in the study of protein structure, stability, and design. Many fluorinated phenylalanine and alanine analogs have been impactful in proteomics thus far, and finding new amino acid analogs and building blocks with unique properties has been highly desirable. Many biochemical companies and academic investigators can benefit from a broad range of fluorinated α-amino acids, and groups have studied the stability of collagen and the amino acid uptake of tumor cells by F18 [Yoder et al. Chemical Society Reviews (2002) 31:335; Laverman et al., European Journal of Nuclear Medicine and Molecular Imaging (2002) 29:681]. In addition, many peptides containing fluorine have been used as anti-microbial peptides (AMPs) to prevent microbial growth [Salwiczek, et al. Chemical Society Reviews (2012) 41:2135; Laverman et al., incorporated supra]. From a commercial standpoint, companies such as AP Bioscience LLC (Princeton, N.J.) offer fluorinated amino acids (see AP Bioscience Product List P #7129596).
Multifluorinated arenes and heteroarenes represent an important motif, owing to the ability of fluorine to substantially alter the performance of molecules in various applications (FIG. 1). However, in sharp contrast to their importance, there is a relative dearth of methods that rapidly yield multifluorinated arenes, and thus, there is a need for methods to access multifluorinated (hetero) arenes.
Therefore, there is a need in the art for new and improved methods of producing these desired types of molecules that overcome the disadvantages and defects of the prior art. It is to such new and improved methods, as well as products produced from said methods, that the present disclosure is directed.